Pathogenesis of autoimmune hypothyroidism induced by lymphokine-activated killer (LAK) cell therapy: in vitro inhibition of human thyroid function by interleukin-2 in the presence of autologous intrathyroidal lymphocytes

Thyroid. Fall 1993;3(3):179-88. doi: 10.1089/thy.1993.3.179.

Abstract

Lymphokine-activated killer (LAK) cell therapy frequently results in primary hypothyroidism. To elucidate the responsible mechanism, we investigated the effects of interleukin-2 (IL-2) on thyroid function of cultured human thyroid follicles in the presence or absence of autologous thyroid-derived lymphoid cells (TDLC). Human thyroid follicles, obtained by subtotal thyroidectomy from patients with Graves' disease, were cultured in serum-free medium containing bTSH and various concentrations of human IL-2, with or without TDLC. After 5 days of culture, 125I was added, and after an additional 3 days of culture, 125I incorporated into thyroid follicles and organic 125I (125I-T4 + 125I-T3) released into the culture medium were estimated. In the absence of TDLC, IL-2 did not affect bTSH-induced thyroid function. In the presence of TDLC, however, IL-2 inhibited the bTSH-stimulated thyroid function in a concentration-dependent manner. The minimum IL-2 concentration required to inhibit thyroid function was 1 U/ml. At 100 U/ml, IL-2 inhibited thyroid function completely. IL-2 increased the concentration of IFN-gamma in the culture medium conditioned by TDLC but not by thyroid follicles. When both were cocultured, IL-2 more significantly increased the concentration of IFN-gamma to an extent sufficient for inhibiting thyroid function per se. Furthermore, the addition of anti-IFN-gamma antibody to the medium partially restored the IL-2-inhibited thyroid function. In summary, by coculturing human thyroid follicles and autologous intrathyroidal lymphocytes with IL-2, it was possible to reproduce the thyroid dysfunction associated with LAK cell therapy. Our data indicate that IL-2 inhibits thyroid function, at least partly, by stimulating production of IFN-gamma, a potent inhibitory cytokine for thyroid cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Cell Communication
  • Cells, Cultured
  • Cytokines / pharmacology*
  • Graves Disease / physiopathology
  • Graves Disease / surgery
  • Humans
  • Immunotherapy, Active / adverse effects*
  • Interferon-gamma / pharmacology
  • Interleukin-1 / pharmacology
  • Interleukin-2 / adverse effects*
  • Interleukin-2 / pharmacology*
  • Interleukin-8 / pharmacology
  • Iodides / metabolism*
  • Iodine / metabolism
  • Iodine Radioisotopes
  • Killer Cells, Lymphokine-Activated*
  • Lymphocytes / physiology*
  • Recombinant Proteins / adverse effects
  • Recombinant Proteins / pharmacology
  • Thyroid Gland / drug effects
  • Thyroid Gland / metabolism
  • Thyroid Gland / physiology*
  • Thyroiditis, Autoimmune / etiology*
  • Thyroiditis, Autoimmune / immunology
  • Thyrotropin / pharmacology
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Cytokines
  • Interleukin-1
  • Interleukin-2
  • Interleukin-8
  • Iodides
  • Iodine Radioisotopes
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma
  • Thyrotropin
  • Iodine